Breaking Barriers: Cultivating a Collaborative Infrastructure in a Hybrid Academic Community Cancer Center

Cultivating an internal collaborative infrastructure is critical for the success of new initiatives that require multi-departmental and multidisciplinary services. Ensuring that the Bio-specimen Repository Facility (BRF) program at Miami Cancer Institute is logistically positioned to continuously enroll participants, collect fit-for-purpose biospecimens, and annotate them with clinical information is critical to support translational research. Five pivotal departments were identified for developing collaborative efforts: Surgery, Infusion Services, Laboratory, Pathology and the Oncology Data Warehouse team. Here we present the dynamic workflows established for patients consented in the clinical areas of Infusion and Surgery, for routine and specific biospecimen collection in the Laboratory and Pathology Departments and for complex data extraction by the Oncology Data Warehouse team. We also dis-cuss strategies used by BRF leadership to interconnect departments and encourage cooperation by focusing on the common goal, presenting issues as a problem-solving opportunity, assigning cross-functional liaisons, developing multi-functional teams for critical launches and nurturing effective communication strategies for increased productivity

ABCA7 frameshift deletion associated with Alzheimer disease in African Americans

Objective: To identify a causative variant(s) that may contribute to Alzheimer disease (AD) in African Americans (AA) in the ATP-binding cassette, subfamily A (ABC1), member 7 (ABCA7) gene, a known risk factor for late-onset AD. Methods: Custom capture sequencing was performed on ∼150 kb encompassing ABCA7 in 40 AA cases and 37 AA controls carrying the AA risk allele (rs115550680). Association testing was performed for an ABCA7 deletion identified in large AA data sets (discovery n = 1,068; replication n = 1,749) and whole exome sequencing of Caribbean Hispanic (CH) AD families. Results: A 44-base pair deletion (rs142076058) was identified in all 77 risk genotype carriers, which shows that the deletion is in high linkage disequilibrium with the risk allele. The deletion was assessed in a large data set (531 cases and 527 controls) and, after adjustments for age, sex, and APOE status, was significantly associated with disease (p = 0.0002, odds ratio [OR] = 2.13 [95% confidence interval (CI): 1.42–3.20]). An independent data set replicated the association (447 cases and 880 controls, p = 0.0117, OR = 1.65 [95% CI: 1.12–2.44]), and joint analysis increased the significance (p = 1.414 × 10−5, OR = 1.81 [95% CI: 1.38–2.37]). The deletion is common in AA cases (15.2%) and AA controls (9.74%), but in only 0.12% of our non-Hispanic white cohort. Whole exome sequencing of multiplex, CH families identified the deletion cosegregating with disease in a large sibship. The deleted allele produces a stable, detectable RNA strand and is predicted to result in a frameshift mutation (p.Arg578Alafs) that could interfere with protein function. Conclusions: This common ABCA7 deletion could represent an ethnic-specific pathogenic alteration in AD

Converging evidence for differential regulatory control of APOEε4 on African versus European haplotypes

INTRODUCTION. The difference in APOEϵ4 risk for Alzheimer disease (AD) between different populations is associated with APOEϵ4 local ancestry (LA). We examined LA SNPs with significant frequency differences between African and European/Japanese APOEϵ4 haplotypes for areas of differential regulation. METHODS. We performed two enhancer Massively Parallel Reporter Assay (MPRA) approaches, supplemented with single fragment reporter assays. We utilized Capture C analyses to support interactions with the APOE promoter. RESULTS. The TOMM40 intron 2 and 3 region showed increased enhancer activity in the European/Japanese versus African LA haplotypes in astrocytes and microglia. This region overlaps with APOE promoter interactions as assessed by Capture C analysis. Single variant analyses pinpoints rs2075650/rs157581, and rs59007384 as functionally different on these haplotypes. DISCUSSION. Both differential regulatory function and Capture C data support an intronic region in TOMM40 as contributing to the differential APOE expression between African and European/Japanese LA. Competing Interest Statement Authors disclosure support from NIH (KN, LW, SG, AG, JY, DD, MV, JV), State of Florida grants (KN, AG, JY, DD), Miami Heart Research Institute (LW), Helping Hands for GAND Foundation (JY). Royalties have been received by JV (Duke University) and JY (Elsevier). Consulting fees have been received by AG (Northwestern University) and JV (University of Pennsylvania). SG receives funds from patents (US Patent Number 10,125,395, 2018; US Patent Number 9,926,600, 2018; US Patent Number 10,066,266, 2018; Canada Patent Number 2,714,713, 2018; US Patent Number 10,266,896, 2019.). JY has contributed to the Helping Hands for GAND Foundation scientific advisory board without compensation. ML, DVB, KC, OO, NH and SR declare no further disclosures